1. Field of the Invention
This invention relates to neutral-tissue stimulation and infusion techniques, and more particularly relates to such techniques for treating epilepsy.
2. Description of Related Art
Epileptic seizures are the outward manifestation of excessive and/or hypersynchronous abnormal activity of neurons in the cerebral cortex. Seizures are usually self limiting. Many types of seizures occur. The behavioral features of a seizure reflect function of the portion of the cortex where the hyper activity is occurring. Seizures can be generalized, appearing to involve the entire brain simultaneously. Generalized seizures can result in the loss of conscious awareness only and are then called absence seizures (previously referred to as "petit mal"). Alternatively, the generalized seizure may result in a convulsion with tonic-clonic contractions of the muscles ("grand mall" seizure). Some types of seizures, partial seizures, begin in one part of the brain and remain local. The person may remain conscious throughout the seizure. If the person loses consciousness the seizure is referred to as a complex partial seizure.
Researchers have developed several lines of evidence in studies with animals to demonstrate the existence of a system which can control the propagation and/or the generation of different kinds of seizures. The involvement of the substantia nigra, a particular portion of the brain considered to be part of neural circuitry referred to as the basal ganglia, was first suggested by Gale (Fed. Proc. 44, 2414-2424, 1985). Considerable evidence has been generated through research to support this observation and was reviewed by Depaulis, Vergnes and Marescaux (Progress in Neurobiology, 1994, 42: 33-52). Researchers have shown that the inhibition of the substantia nigra will increase the threshold for seizure occurrence in experimental animal models of epilepsy.
Neuroscientists now have a better understanding of the neural connections that make up the basal ganglia. These connections are reviewed by Alexander et. al. (Alexander, Crutcher, and DeLong, "Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, `prefrontal` and `limbic` functions." Prog. Brain Res. 85: 119-146.). The substantia nigra receives input from the subthalamic nucleus (STN) which is excitatory and involves glutamate as the neurotransmitter conveying information at the synapse. Bergman et al. have shown that a lesion of the subthalamic nucleus will reduce the inhibitory output of the internal segment of the globus pallidus and substantia nigra reticulata (SN) (H. T. Bergman, T. Wichmann, and M. R. DeLong, 1990, Science, 249: 1436-1438). The subthalamic nucleus receives input from the external segment of the globus pallidus (GPe). This input is inhibitory using GABA as a transmitter substance. Hence, increased activity of the neurons in GPe will increase inhibition of neurons in the subthalamic nucleus which will reduce the excitation of neurons in the substantia nigra.
Neurosurgeons have been able to diminish the symptoms of many neural disorders by lesioning certain brain areas. Lesions of the ventral lateral portion of the internal Globus Pallidus and Vim Thalamus can alleviate certain disorders of movement. In addition, it has been demonstrated that open-loop Deep Brain Stimulation (DBS) at high frequencies (100 Hz. or higher) of certain brain structures can alleviate, diminish, or completely stop symptoms of tremor, rigidity, akinesia or hemiballism much like creating a lesion. Published targets of stimulation include the VIM (ventral intermediate thalamus), subthalamic nucleus, and internal globus pallidus.
Benabid et al. (The Lancet, Vol 337: Feb. 16, 1991, pp 403-406) have shown that stimulation of the Vim nucleus of the Thalamus will block tremor. In this instance, stimulation at frequencies around 100 to 185 pulses per second accomplishes the same physiological response as a lesion of this region. Benabid's research team has extended this work to stimulation of the subthalamus in order to help reduce symptoms of motion disorders ("Vim and STN Stimulation in Parkinson's disease", Movement Disorders, Vol 9, Supplement 1(1994); "Effect on Parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation", The Lancet, Vol 345, Jan. 14, 1995.) It has been known for some time that electrical stimulation of neurons at lower stimulus pulse frequencies will activate the neurons.
Electrical stimulation of the nervous system has been used to suppress seizures. Cooper et. al. have stimulated the cerebellum ["The Effect of Chronic Stimulation of Cerebellar Cortex on Epilepsy in Man", I. S. Cooper, I. Amin, S. Gilman an J. M. Waltz in The Cerebellum, Epilepsy and Behavior, Cooper Riklan and Snider ed. Plenum Press, NY, 1974] Velasco et. al. have stimulated Centre Median nucleus of the thalamus [Electrical Stimulation of the Centromedian Thalamic Nucleus in control of Seizures: Long-Term Studies, F. Velasco, M. Velasco, AL Velasco, F Jimenez, I Marquez, and M. Rise, Epilepsia, 36(1): 63-71, 1995] Sussman et. al. have stimulated the anterior nucleus of the thalamus to treat epilepsy [Sussman N M, Goldman H W, Jackel R A, "Anterior Thalamic Stimulation in Medically Intractable Epilepsy Part II: Preliminary Clinical Results", Epilepsia 1988; 29: 677]. Durand electrically stimulated the focus of seizure origin to inhibit synchronized neuronal activity in the hippocampal slice model [Durand, D. "Electrical Stimulation Can Inhibit Synchronized Neuronal Activity", Brain Research: 382: 139-144, 1986., Durand, D. and Warman E., Desynchronization of Epileptiform Activity by Extracellular Current Pulses in Rat hippocampal Slices, Journal of Physiology (1994), 480.3] More recently Schiff et. al. used chaos theory to apply stimulation to a seizure focus to abort the seizure[ S. Schiff, K. Jerger, D Duong, T. Chang, M. Spano & W Ditto, "Controlling Chaos in the Brain", Nature, Vol 370, Aug. 25, 1994].
Infusion of certain drugs into a region of the brain can affect the excitability of the neurons at the site of infusion. Smith et. al. infused lidocaine hydrochloride into the focus of rats with focally induced generalized seizures showing the seizure could be suppressed [Douglas Smith, Scott Krahl, Ronald Browning and Edwin Barea, "Rapid Cessation of Focally Induced Generalized Seizures in Rats Through Microinfusion of Lidocaine Hydrochloride into the Focus", Epilepsia, 34(1):43-53, 1993] Depaulis et. al. [Brain Research, 498 (1989) 64-72] have infused muscimol into the substantia nigra of rats suppressing the occurrence of spike-and-wave discharges in animal models of non-convulsive epilepsy. Mirski, McKeon, and Ferrendelli [Brain Research, 397 (1986) 377-380] showed that infusion of an inhibitor of GABA transaminase into the anterior thalamic nucleus protected rats against PTZ induced generalized seizures but not those caused by maximal electroshock while infusion of the agent into the substantia nigra had the opposite effect.
Researchers have devised algorithms to detect the onset of a seizure. Qu and Gotman report a system that recognizes patterns of electrical activity similar to a template developed from recording an actual seizure. [H. Qu and J. Gotman, "A Seizure Warning System for Long-term Epilepsy Monitoring", Neurology, 1995; 45: 2250-2254.] Osario et. al. have reported an algorithm applied to signals recorded from intracranial electrodes capable of 100% seizure detection rate with 0% false negatives and minimal false positives. [I. Osario, M. Frei, D. Lerner, S. Wilkinson, "A Method for Accurate Automated Real-time Seizure Detection", Epilepsia, Vol. 36, Suppl. 4, 1995].